The traditional classification of neurodegenerative disorders into discrete diseases has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. A clinical continuum is particularly notable for neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins. Patients can have a mixture of cognitive, language, and motor symptoms. Examples of these disorders include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), primary progressive aphasia (PPA), and HD-negative Huntington. Some causative genes have been found for each disorder, although most patients have sporadic disease. Interestingly, the same genetic mutation can produce different clinical phenotypes. The link between the gene mutations and pathology in these disorders may lie in the molecular and cellular processes affected by mutant gene products. As the field of neurology moves more towards the molecular characterization of neurodegenerative disorders, there is a need to understand clinical phenomenology in the context of pathology and genetic or epigenetic defects that are the drivers of disease. Given the broad spectrum of neurological symptoms in this family of disorders, the goal of this clinic is to bring together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. The objective is to gain knowledge that will set the stage for precision medicine in which therapy will be tailored to the underlying cause of each patient's disease. In FY19, a screening clinic has been held each month to evaluate patients with complex neurodegenerative disorders referred by neurologists, both from the local community and throughout the US. The staff of the clinic arrange clinical studies that help to establish the diagnosis, as well as a standard battery of clinical and cognitive testing. Patients have the option of giving biospecimens for research purposes. Each month, the clinic holds a multidisciplinary conference with neurologists, neuropsychologists, and health personnel involved in the clinic to discuss individual patients and their diagnosis and suitability for research protocols. Patients who are found to be eligible for ongoing research studies are referred to those studies. Otherwise patients may sign up for a registry for receiving information on future NIH studies and an annual questionnaire to update their current status and continued interest.